Genetics Flashcards
1
Q
Terms
- Heteroplasmy
- Variable expression
- Incomplete penetrance
- Loss heterozygosity
- Imprinting
- Pleiotropy
- Anticipation
- Mosaicism
A
- we have 2 types gnetic material, nuclear DNA and mito DNA
- 2 people with same mutation look differently
- even though genotype shows mutation not everyone shows it phenotypically
- need 2 mutations in order to become dangerous -> CA
- one chromosome is silenced and other chromosome has mutation
- one mutation presents with problems in multiple systems (marfans)
- severity of dx is worse and age of presentation is earlier with each generation
- not all cells have the mutation, so some cells normal and others have problem
2
Q
How to figure out pedigree
- affect mult gen w/ male to male transmission
- affect mult gen w/o male to male transmission and males pass to all daughters
- does not affect all gen and affects both males and females
- does not affect all gen and affects mostly males
- all children of affected female have it but none of the children from affected male have it
A
- auto dom
- X-linked dom
- auto recessive
- X-linked recessive
- mitochondrial
3
Q
AD characteristics
- what is affected?
- generations affected?
- onset
A
- structural proteins
- all
- late
4
Q
AR characteristics
- what is affected
- onset
- generations affected?
A
- enzymes
- early
- skips
5
Q
XLR characteristics
- pts at risk
- transmission
- generations
A
- male bc only have one X so not as protected as females
- no male to male transmission
- skips
6
Q
XLD characteristics
- pts at risk
- transmission
- generations
A
- male
- no male to male, but a;; male pass to daughters and all females can pass to daughters and sons
- does not skip generations
7
Q
Mito inhertiance
- who is affected
- sxs
A
- all children of affected female but no children of affected male
- neuropathies and myopathies
8
Q
Auto Dom DX
- Very (2)
- Powerful
- Likable
- ReSpectable
- D
- O (2)
- M
- I
- N
- A (2)
- N
- T (2)
- Humans (7)
- get Jobs
A
- Von willdebrand and Von Hippel
- Pseudo hypoparathyroidism
- Li-Fraumeni
- RB, Sturge Weber
- Dystrophia myotonica
- Osteo imperfects and Osler weber
- Marfans
- Intermittent porphyria
- Neurofibromatosis
- Achondroplasia and Adult polycystic kidney
- Noonan syndrome
- Tuberous scelrosis, tremor
- Hypercholesterol, HCM, Hereditary spherocytosis, hereditary non polyposis, hereditary hemmorrhagic telangectasia, Huntingtons, Hypokalemic periodic paralysis
- Job syndrome
9
Q
Job syndrome
- also known as
- gene
- problem
- sxs (FATED)
- skeleton sxs
A
- Hyper IgE
- STAT3
- decrease INF gamma by Th1
- coarse face, abcess, teeth, high IgE, derm problems (eczema)
- scoliosis and osteopenia
10
Q
Li Fraumeni Syndrome
- what is it
- caused by
- inheritance
- sxs
- family hx
- types
A
- genetic predisposition to early dev of CA
- mutation in p53 -> allows for progression to S phase even w/ DNA damage
- one mutant allele and then damage to 2nd allele
- development of malignant tumors in people younger than 45
- mult CA in ppl younger than 45
- breast, adrenal, brain, blood
11
Q
Acute Intermittent Porphyria
- what is it
- caused by
- sxs
- precipitated by
A
- heme production disturbed
- phorphobilinogen deaminase deficiency
- abd pain, peripheral neuropathy, CNS signs, port wine urine, w/o rash
- drugs
12
Q
Von Hippel Lindau
- gene
- causes
- DX
- management
A
- VHL gene
- accumulation of HIF-1a which is usually made when hypoxic and increases EPO and VEGF
- family history + hemangioblastoma OR renal cell carcinoma
- routine screening for tumors w/ early recognition and symptomatic tx
13
Q
Von Willebrand
- what is it
- types 1,2,3
- chrom
- pathway
- sxs
- DX
- TX for 1 and 2a
- TX for 2b and 3
A
- VWF deficiency
- 1: AD, quantitative defect; 2a: AD, qualitative defect; 2b: hyperbinding of vWF to platelet; 3: AR, absence of vWF
- 12
- vWF from endo cannot bind onto GpIb to allow for platelet yo expose GpIIb-IIIa for binding to other platelets to create platelet meshwork
- superficial bleeding (nose, bleeding gum, heavy period, easy bruising)
- measure quantity of vWF with assay, measure function of vWF with Ristocetin assay (only causes aggregation in presence of vWF),
- Desmopressin -> stimulates release of vWF from weibel palade bodies of endo cells
14
Q
Essential tremor
- worsens
- commonly located in
- classically improved by
- management
A
- w/ activity
- UE
- EtOH consumption
- propanolol -> beta blocker -> decrease muscle responding
15
Q
Retinoblastoma
- what is it
- mutation
- pathway
- screening
- sxs
A
- retinal CA
- mutation of RB1 on chrom 13
- RB continuously phosphorylated by CDk2-cyclin A complex causing it to stop inhibiting E2F and allowing for continuation of cell cycle from G1 to S
- red reflex
- leukocoria, decrease in vision, irritation of eye, glaucoma, strabisumus
16
Q
Marfans
- mutation of
- protein affected
- heart findings
- lung complications
- spine complications
- pehno sxs
- eye complications
- marfanoid syndromes
A
- Fb1 on chrom 15
- fibrillin-1 glycoprotein -> part of ECM and causes abnormal elastin
- thoracic aortic aneursym
- spontaneous pneumo
- dural ectasia -> weakened dural sac that causes back pain
- tall, arachnodactyly,
- lens dislocation
- homocysteinuria, ehler danlos, sticklers (flat face, myopia, cleft palate), MEN2b
17
Q
Osteogenesis Imperfecta
- what is it
- biochem problem
- sxs
A
- deficiency of type 1 collagen causing bone fragility
- glycine replaced with bulky AA
- bone fragility, loose joints, poor muscle tone, blue sclera
18
Q
Osler- Weber- Rendu
- also known as
- causes
A
- hereditary hemmorrhagic telangiectasia
- blood vessel disorder in skin, mucous membranes of lips/ oronasopharynx/ resp tract / GI tract/ GU tract/ brain/ liver/ spleen
19
Q
Familial Hypercholesterolemia
- mutation of
- location
- findings
- high risk of
- family hx
A
- LDLR gene
- chrom 19
- xanthelasma and thendon xanthomas
- CAD, MI
- healthy family w/ members who have died young from MI
20
Q
Huntingtons
- What is it, gene affected, chromosome
- what AA
- causes
- gross
- sxs
A
- Tri nuc repeat of CAG on HTT gene on chrom 4
- CAG codes for glutamine
- repressed / silenced transcription of other genes
- caudate atrophy
- chorea (writhing motion), abnrml facial expressions and inability to stop and start actions, aggression, depression, loss of cognitive planning and thinking and memory
21
Q
Hypokalemic periodic paralysis
- caused by
- type 1: type of channel, chrom
- type 2: type of channel, chrom
- sxs
- location
- when
- trigger
- tx
A
- rapid drops in blood potassium
- CACNA1S voltage gated Ca channel in T tubule, chrom 1
- SCN4A voltage gated Na channel in NMJ, chrom 17
- muscle weakness and transient paralysis (hours to days)
- hips or shoulders
- begin in adolescence and occurs after exercise
- EtOH and high carb/ Na meals
- focus on preventing future attacks and avoid triggers
22
Q
Achondroplasia
- caused by
- sxs
A
- glycine replaced with arginine in FGFR3 gene
- frontal and parietal bossing, short nose, normal torso length w/ short limbs
23
Q
Adult Polycystic Kidney Dx
- presents
- mutations
- sxs
A
- between 30 and 40 yrs old
- PKD1 (chrom 16, reg of cell cylce and Ca transport in epi cells), PKD2, PKD3
- back pain, UTI, renal colic, nephrolithiasis and cysts on kidneys
24
Q
Hereditary Spherocytosis
- caused by
- shape
- MCHC
- RDW
- Osmotic fragility
A
- mutation in ankyrin which attaches proteins to apectrin membrane skeleton
- sphere shaped RBS w/o central pallor
- MCHC: concentration of hemoglobin in RBC -> increased
- RDW: variation in size of RBC -> increased bc have variable sizes of RBC in this dx
- RBC will lyse under stress from water pulling on their membranes
25
Q
Sturge- Weber syndrome
- type of disorder
- gene
- caused by
- skin sxs
- neuro sxs
- ocular sxs
A
- neuro- oculo- cutaneous syndrome
- GNAQ gene - chrom 9
- embryo developmental anomaly and malformation of blood vessels in pia mater
- port wine stain on forehead or upper eyelid on one side of face
- seizure in infancy w/ muscle weakness on side of body opp bithmark; developmental and cognitive delay
- 50% will have glaucoma
26
Q
Tuberous Sclerosis
- what is it
- mutation of
- causes
- needs
- location
- sxs
A
- multi- organ disorder that allows for non-malignant tumors to grow abundantly
- TSC1 and TSC2 -> Hamartin and tuberin
- Hamartia (malformed issue) and Hamartomas (benign growth)
- 1 inherited copy and other mutated copy
- heart, kidney, eye, lung, skin, brain
- seizures, developmental difficulties, autism, ash leaf spot (hypomelanin)
27
Q
Schwannoma
- other name
- location
- c8 compression
- c7 compression
- c5 compression
- increased risk of
A
- Neurofibromatosis 2
- cerebellopontine angle
- can cause cochlear (sensorineural hearing loss) or vestibular problems (vertigo, nystagmus)
- paralysis of facial expression muscles and taste in ant 2/3 tongue
- loss sensation around mouth, nose, and corneal reflex, w/ paralysis of muscles of mastication
- meningioma and ependymomas
28
Q
Myotonic Dystophy
- what is it
- type disorder
- main problem
- other problems
- type 1: name, gene, chrom, repeat, location, prognosis, characteristics, endo problems
- type 2: name, gene, chrom, repeat, location, systemic disorders
A
- chronic, slowly progressive muscle disease
- Tri nuc repeat (CTG)
- progressive wasting and weakness of muscles w/ prolonged muscle contraction
- cardiac, endocrine, visual
- severe congenital form, DMPK gene, chrom 19, CTG, muscle weakness in face/ neck/ hands/ lower legs, slowly progresses, long face w/ hanging jaw, DM
- proximal myotonic myopathy, CNPB gene, chrom 3, CCTG, muscle weakness in hips/ elbow/ shoulder/ neck, systemic disorder absent
29
Q
Familial Adenomatous Polyposis
- gene
- findings, what age
- sequlae
A
- APC -> normally suppresses tumors
- numerous polyps develop from intestine epi in teenage years
- polyps will become malignant unless removed
30
Q
Alkaptonuria
- deficiency of
- mutation of
- can’t
- build up
- findings infant
- findings adult
- outcome
A
- homogentisic acid oxidase
- HGD gene
- break down tyrosine and phenylalanine
- homogentisic acid
- dark urine when standing or when ferric chloride added
- arthritis, dark spots on sclera or cornea, dark ear
- good
31
Q
Ataxia Telangiectasia
- defect in
- gene
- affects
- findings
A
- DNA repair and cell division
- ATM
- nervous system and immune system
- ataxia before 5, chorea, chronic sinopulm infections, increase CA risk (leukemia and lymphoma), telangectasia in eyes and skin, oculomotor apraxia
32
Q
Albinism
- caused by
- normal function
- affects
A
- tyrosinase deficiency
- tyrosine -> dopa -> melanin
- eye and skin
33
Q
Alpha- 1- antitrypsin def
- what is it
- type of emphysema
- other sxs
A
- loss of protection for liver and lungs from tissue destroying proteases
- panacinar
- pulm (chronic lung infection, SOB) and hepatic findings
34
Q
Beta Thalassemia
- gene, chrom
- minor vs major
- intermedia
A
- HBB gene on chrom 11
- minor is one gene missing (under production of beta chain) and major is both genes missing (severe anemia ensues)
- mutation in kozak sequence of beta globin gene w/ hypochromic, microcytic anemia
